This Program Project deals with protein structure, function, and engineering. Five members of the MIT tenured staff are principal investigators of the Program. Emphasis is placed upon the integration of molecular biology, mutagenesis, and recombinant DNA technology with the manipulation and determination of protein structure. Because many of the individual efforts include common technologies, a core facility will be established. This facility will serve the needs of and integrate the projects of all members of the Program. Specific areas of research include the design of antibody binding sites, the nature of antigenic sites on protein and nucleic acid surfaces, the capacity of protein structure for redesign of active sites, and the delineation of structural motifs in protein nucleic- acid interactions. These investigations can lead to a deeper understanding of protein design and of the capacity of proteins to be reengineered for specific applications in the health sciences.